Phase I study of twice-weekly gemcitabine and concurrent thoracic radiation for patients with locally advanced non-small-cell lung cancer

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity of twice-weekly gemcitabine and concurrent thoracic radiation in patients with Stage IIIa/IIIb non-small-cell lung cancer (NSCLC). Methods and Materials: Seventeen patients with histologically confirmed Stage IIIa and IIIb NSCLC were studied. Genicitabine was administered via a 30-min i.v. infusion twice weekly for 6 weeks concurrent with 60 Gy of thoracic radiation. Gemcitabine, starting at a twice-weekly dose of 10 mg/m(2) (20 mg/m(2)/week), was escalated in 10-15 mg/m(2) increments in successive cohorts of 3 to 6 patients until dose-limiting toxicity was observed. Results: Of the 17 patients entered, 16 were evaluable for toxicity. The dose-limiting toxicity at 50 mg/m(2) given twice weekly (100 mg/m(2)/week) was Grade 3 pneumonitis observed in 1 patient, Grade 3 pulmonary fibrosis in a second patient, and Grade 4 esophagitis observed in two additional patients. Twice-weekly gemcitabine at a dose of 35 mg/m(2) was determined to be the MTD. The overall response rate for the 16 evaluable patients was 88%. The median survival for the entire group is 16.0 months. Conclusions: The MTD of twice-weekly gemcitabine is 35 mg/m(2) (70 mg/m(2)/week) given with thoracic radiation. A Phase II study within the Cancer and Leukemia Group B to ascertain the potential efficacy of this treatment regimen is in development. (C) 2001 Elsevier Science Inc.